马全红教授在Neuroscience Letters上发表题为TDP-43 interaction with the intracellular domain of amyloidprecursor protein induces p53-associated apoptosis的论文。
Abstract: TAR DNA-binding protein 43 (TDP-43), an essential pathological protein in both amyotrophic later sclero-sis (ALS) and frontotemporal lobar degeneration (FTLD), is expressed abnormally in Alzheimer’s disease(AD). However, whether and how TDP-43 contributes the pathogenesis of AD remains unknown. We haveshown here a colocalization between TDP-43 and the intracellular domain of APP (AICD) in the nucleus.Coimmunoprecipitation analysis showed an interaction between TDP-43 and AICD. Overexpression ofTDP-43 in COS7 cells enhanced the transactivation of AICD in an APP-Gal4 luciferase reporter system.Real-time PCR analysis showed that cotransfection of TDP-43 and AICD in HEK293 cells increased P53mRNA levels compared to either TDP-43-transfected or AICD-transfected cells. Moreover, cotransfectionof TDP-43 and AICD in either N2a or COS7 cells showed increased numbers of apoptotic cells comparedto either TDP-43-transfected or AICD-transfected cells, indicating that TDP-43 enhances AICD-mediatedapoptosis in N2a or COS7 cells. Thus, TDP-43 may play a role in AD pathology through interaction withAICD.
